GLP-1 Obesity Drugs and Addiction Treatment: Semaglutide and Tezepetide in Alcohol and Opioid Use Disorders

GLP-1 receptor agonists such as semaglutide and tirzepatide, traditionally used for diabetes and obesity, are being investigated as potential treatments for addiction. This Nature long read traces how these drugs may blunt cravings for alcohol, opioids, and other substances by acting on brain reward pathways, supported by early clinical data and neuroimaging. It also outlines the evolving trial landscape, regulatory hurdles, and safety considerations, while highlighting how weight loss effects could influence addiction outcomes. The piece follows researchers like Sue Grigson and colleagues as they test these therapies in diverse populations, offering a cautious but hopeful view of a possible new direction in addiction medicine.

Overview

GLP-1 receptor agonists, including semaglutide and tirzepatide, are being explored beyond diabetes and obesity as potential treatments for addiction. The Nature long read traces early anecdotes, clinical data, and the mechanistic rationale linking GLP-1 signaling to reward circuits in the brain. It highlights how these drugs could dampen cravings for alcohol, nicotine, opioids, and other substances by modulating brain pathways that govern reward and motivation, with implications that extend to mood and cognitive function.

"People are feeling hopeful, and that's a good thing." - Sue Grigson, neuroscientist

Brain Mechanisms and Pharmacology

The piece explains that GLP-1 receptors are present in key brain regions involved in reward processing, such as the ventral tegmental area and nucleus accumbens, as well as in gut and pancreas signaling that influences appetite. When GLP-1 drugs mimic natural signaling, they can blunt dopamine responses to rewarding cues, reducing the urge to repeat addictive behaviors. The narrative emphasizes the consistency of these effects across substances and how stress systems interact with GLP-1 signaling to mitigate withdrawal and craving. "the neurobiological system that is activated by rewarding substances, food, sex, drugs, rock and roll, it's the same system." - Roger McIntyre

Clinical Trials and Evidence

Early human trials have produced mixed results for older GLP-1 compounds, but recent high-potency drugs like semaglutide show more promise in reducing consumption and cravings in alcohol and opioid use disorders. Researchers are coordinating multiple trials across dose and delivery methods to determine who benefits most and under what conditions. The article notes that regulatory approval for a new addiction medicine class remains uncertain, underscoring the need for robust, reproducible outcomes that translate into real-world benefits. "it's a revolution." - Elizabeth Jurlogholm

In addition, imaging studies using fMRI suggest GLP-1 therapies dampen reward-related brain activity in response to cues, offering a biomarker-driven route to understanding efficacy and identifying responders. Clinicians caution that weight-related effects, dietary considerations, and potential nutritional risks must be carefully monitored in addiction populations already prone to irregular eating patterns. "We've never seen this before." - Heath Schmidt

Regulatory, Safety, and Broader Implications

Despite growing interest, experts emphasize that the road to regulatory acceptance is long. Trials must demonstrate meaningful reductions in consumption and relapse risk, not just changes in brain activity or craving. The discussions also consider broader uses, including dementia and mood disorders, reflecting the overlap between reward circuitry, learning, and cognition. The piece concludes with cautious optimism about GLP-1 therapies, paired with vigilance regarding safety and the complex social context of addiction treatment.

"No truly new class of addiction medicine has won approval from regulators in decades." - Elizabeth Jurlogholm